The long-term objective of this proposal is to build capacity for translational research (transfer of basic research findings to clinical practice) in Maine's biomedical research infrastructure, by creating partnerships between strong basic and clinical researchers. Maine has considerable existing strength at The Jackson Laboratory (TEL) in basic research on the genetics of the mouse. Recent advances in the ability to manipulate the mouse genome have made the mouse a powerful mammalian model for human genetic diseases. Mice can serve as hosts for human genes and tissues. The conservation in mouse and human genome organization makes research on homologous disease-related genes possible. To exploit these advances in mouse genetics, TEL's scientists must forge new collaborations with clinical researchers. Partners are needed for a) parallel research on homologous diseases; b) assistance in developing and evaluating appropriate mouse models; and c) identifying important disease-related genes conserved in mice and humans. This application describes a plan to use the expertise and genetic resources at TEL as a magnet to increase biomedical research strength among clinical partners. The goal of increasing collaborative research in Maine fits well with the aims of the IDeA program, to increase, strengthen and sustain competitive research capacity in eligible states. TEL, as the lead institution for the IDeA program, has identified a set of focus areas in which there are existing clinical and basic strengths. These include atherosclerosis, osteoporosis, cancer, and cystic fibrosis. Within each focus group, a collaborative pilot project is presented. The atherosclerosis project will recruit families with an atherosclerosis-resistant phenotype, hyperalphalipoproteinemia (HALP) and test linkage of HALP with specific candidate genes. The osteoporosis project will identify genes and hormones that regulate attainment of peak bone mass, using inbred and mutant mouse strains as experimental models. In cancer, unique immunodeficient mutant stocks will be used to develop a mouse model for human breast cancer metastatic disease suitable for testing therapies based on bioresponse modifiers. Cystic fibrosis (CF) research focuses on the functional consequences of CF mutations found in Maine's patient populations, using in vitro assays and transgenic mice. These projects will facilitate technology and information transfer among Maine institutions, provide training in research design and grantsmanship for young investigators, and add technical expertise and capacity in specified areas. Each focus group also included a networking/planning phase designed to foster future collaborative research. The specific aims of this proposal are: a) to increase capacity of clinical collaborators to conduct biomedical research and to obtain independent, competitive funding; b) to recruit new faculty who will bring expertise needed for proposed research; c) to develop animal models of clinically relevant disease at TEL; d) to increase capacity to translate basic research findings to clinical practice; and e) to conduct comparative analyses including identifying homologous genes involved in mouse and human disease and validating mouse models of human diseases.